Most men with advanced prostate cancer, whether initially treated through surgical or chemical castration, eventually develop drug-resistant tumors. Monitoring for drug resistant genetic mutations could inform selection of the next line of therapy. Complicating this is that prostate cancer frequently metastasizes extensively in the bone, which means monitoring may require repeated and sometimes painful bone biopsies, some of which may fail to recover a tumor sample.
A new non-invasive, "no cell left behind" approach developed by Epic Sciences, which monitors tumor cells circulating in patients’ blood, may be as effective at biomarker characterization as invasive surgical biopsies for metastatic castration-resistant prostate cancer (mCRPC) patients. This finding is reported in a clinical study led by The Institute of Cancer Research, London, The Royal Marsden NHS Foundation Trust and Genentech, and published in the British Journal of Cancer.
“PTEN loss results in activation of the PI3K/AKT pathway and therefore is an important biomarker for determining sensitivity to inhibitors of this pathway. In this study, we evaluated whether assessment of PTEN through a simple blood draw using a novel technology from Epic Sciences could reflect the current status of PTEN in the patient’s tumor,” says Elizabeth Punnoose, Ph.D., Senior Scientist, Oncology Biomarker Development at Genentech and lead author on the study.
In the study, regular blood draws from 76 mCRPC patients were shipped to Epic Sciences’ CLIA-certified laboratory in San Diego. Fresh metastatic tumor biopsies or archived surgical tumor biopsies, when available, were obtained and analyzed along with the circulating tumor cells (CTCs) in patients’ blood for various genetic, proteomic, and morphological markers, including for the loss of the tumor suppressor PTEN gene. A loss of the PTEN gene occurs in up to half of prostate cancer patients, resulting in resistance to androgen therapies and poor prognosis.
The authors found that the CTCs in patients’ blood detected by Epic Sciences were an “accurate representation” of the genetic aberrations found in fresh metastatic tumor samples surgically biopsied from the patients at the same time. Thus, the authors concluded that the platform “could potentially be used as a non-invasive and real-time solution for biomarker characterization in CRPC.” Furthermore, loss of PTEN in CTCs was found to be prognostic and associated with poorer survival.
Tumor samples collected 5.1 years before this study (median age, archived tumors) were also analyzed. The researchers found discordance between PTEN status in the matched archival tissue and the CTCs from a recent liquid biopsy, illustrating the importance of monitoring how cancer changes over time and in response to the selective pressure of drugs.
“This study underlines the potential of analyzing CTCs from blood samples to uncover emerging genetic mutations in prostate cancer — which will soon allow targeted treatments to be matched to men more effectively in the clinic. In particular it highlights a role for these ‘liquid biopsies’ in trials of AKT inhibitors in advanced prostate cancer,” says Professor Johann S. de Bono, M.D., Ph.D., Head of Drug Development at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust.
“Liquid biopsy holds significant promise as a substitute for invasive tissue biopsies to monitor cancer. Epic Sciences’ liquid biopsy platform allows profiling of individual tumor cells that are driving a patient’s cancer in real-time, thus providing invaluable information for the selection of the relevant combination of drugs at the right points in time,” says Murali Prahalad, Ph.D., President and CEO of Epic Sciences.
Epic Sciences’ "no cell left behind" liquid biopsy technology works by imaging many millions of cells in a blood draw to detect any CTCs. Epic Sciences uses a novel selection-free methodology to identify those CTCs, which enables detection of all categories of rare cancer cells, regardless of adherence to textbook expectations such as cell size or specific cell surface markers. The selection-free approach, according to Prahalad, ensures no important cancer cell is left behind due to a bias in a test.
“To have a comprehensive view of the tumor cells in blood that are actively spreading disease, we need to capture every possible cancer cell. As not all tumor cells share the same abnormalities that confer drug resistance or susceptibility, it is thus instructive to analyze every individual tumor cell for its potentially unique response to a therapeutic regimen,” says Prahalad.
Reference: Punnoose, E et al. PTEN loss in circulating tumor cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients. British Journal of Cancer. Advance Online Publication: September 17, 2015. DOI:10.1038/bjc.2015.332
About Epic Sciences
At Epic Sciences, we develop clinically proven predictive tests to detect and monitor cancer at the individual cell level. With a proprietary rare-cell detection engine, we provide insights to clinical, biotech, pharmaceutical and academic teams on how cancer emerges, mutates and remits so they can make pivotal decisions at every point in patient treatment with greater certainty. Recognizing the unique nature of each person’s cancer, we offer truly personalized diagnostic tests, while being non-invasive for the patient.
We have developed the first clinically proven predictive test for metastatic castration-resistant prostrate cancer (mCRPC), the Epic AR-V7 test. Using the same rare-cell detection platform and Epic’s biobank of over 30,000 blood samples, each profiled with predictive biomarkers, we partner with leading pharmaceutical and biotechnology companies, major cancer centers, the National Cancer Institute (NCI), and the National Institutes of Health (NIH) to pursue additional predictive tests for breast, ovarian, colon and other cancers and diseases. Our mission is to revolutionize cancer care and therapies to make them as precise, safe and life-sustaining as humanly possible.
For more information, visit epicsciences.com.
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